Despite recent technological advances allowing for quantitative single-photon emission computed tomography (SPECT), quantitative SPECT has not been widely used in the clinical practice. The aim of this study is to evaluate the feasibility of quantitative SPECT for measuring metastatic bone uptake in breast and prostate cancer by comparing standard uptake values (SUVs) measured with 99mTc-HDP SPECT/CT and 18F-NaF PET/CT. Twenty-six breast and 27 prostate cancer patients at high risk of bone metastases underwent both 99mTc-HDP SPECT/CT and 18F-NaF PET/CT within 14 days of each other. The SPECT and PET data were reconstructed using ordered-subset expectation-maximization algorithms achieving quantitative images. Metastatic and benign skeletal lesions visible in both data sets were identified, and their maximum, peak, and mean SUVs (SUVmax, SUVpeak, and SUVmean) were determined. SUV ratios (SUVRs) between the lesions and adjacent normal appearing bone were also calculated. Linear regression was used to evaluate the correlations between the SUVs of SPECT and PET and Bland-Altman plots to evaluate the differences between the SUVs and SUVRs of SPECT and PET. A total of 231 skeletal lesions, 129 metastatic and 102 benign, were analyzed. All three SUV measures correlated very strongly between SPECT and PET (R2 ≥ 0.80, p < 0.001) when all lesions were included, and the PET SUVs were significantly higher than SPECT SUVs (p < 0.001). The median differences were 21%, 12%, and 19% for SUVmax, SUVpeak, and SUVmean, respectively. On the other hand, the SUVRs were similar between SPECT and PET with median differences of 2%, − 9%, and 2% for SUVRmax, SUVRpeak, and SUVRmean, respectively. The strong correlation between SUVs and similar SUVRs of 99mTc-HDP SPECT/CT and 18F-NaF PET/CT demonstrate that SPECT is an applicable tool for clinical quantification of bone metabolism in osseous metastases in breast and prostate cancer patients.

Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors. Patients and Methods: TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123. The primary endpoint was safety by adverse events (AE), laboratory values, vital signs, and electrocardiograms. Secondary endpoints included tumor response, pharmacokinetics, and predictive biomarkers. Results: Twenty patients were enrolled, with a median age of 58 years. Most prevalent cancer types included sarcomas (35%), melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were observed. The most frequent treatment-related AEs included fever (16.7%), chills (13.0%), and fatigue (9.3%). Ten patients were evaluable for response on day 78 with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST(20%of evaluable patients). Tumor size reductions occurred in both injected and non-injected lesions. TILT-123 was detected in injected and non-injected tumors, and virus was observed in blood after intravenous and intratumoral injections. Treatment resulted in reduction of lymphocytes in blood, with concurrent lymphocyte increases in tumors, findings compatible with trafficking. Conclusions: TILT-123 was safe and able to produce antitumor effects in local and distant lesions in heavily pre-treated patients. Good tolerability of TILT-123 facilitates combination studies, several of which are ongoing (NCT04217473, NCT05271318, NCT05222932, and NCT06125197). See related commentary by Silva-Pilipich and Smerdou, p. 3649

Background: High-grade gliomas (HGGs) express somatostatin receptors (SSTR), rendering them candidates for peptide receptor radionuclide therapy (PRRT). Our purpose was to evaluate the potential of ⁶⁸Ga-DOTA-1-Nal³-octreotide (⁶⁸Ga-DOTANOC) or ⁶⁸Ga-DOTA-Tyr³-octreotide (⁶⁸Ga-DOTATOC) to target SSTR subtype 2 (SSTR₂) in HGGs, and to study the association between SSTR₂ expression and established biomarkers. Methods: Twenty-seven patients (mean age 52 years) with primary or recurrent HGG prospectively underwent ⁶⁸Ga-DOTA-peptide positron emission tomography/computed tomography (PET/CT) before resection. Maximum standardized uptake values (SUVmax) and receptor binding potential (BP) were calculated on PET/CT and disruption of blood–brain barrier (BBB) from contrast-enhanced T1-weighted magnetic resonance imaging (MRI-T1-Gad). Tumor volume concordance between PET and MRI-T1-Gad was assessed by Dice similarity coefficient (DC) and correlation by Spearman’s rank. Immunohistochemically determined SSTR₂ status was compared to receptor imaging findings, prognostic biomarkers, and survival with Kruskal-Wallis, Pearson chi-square, and multivariate Cox regression, respectively. Results: All 19 HGGs with disrupted BBB demonstrated tracer uptake. Tumor SUVmax (2.25 ± 1.33) correlated with MRI-T1-Gad (r = 0.713, P = 0.001) although DC 0.41 ± 0.19 suggested limited concordance. SSTR₂ immunohistochemistry was regarded as positive in nine HGGs (32%) but no correlation with SUVmax or BP was found. By contrast, SSTR₂ expression was associated with IDH1 mutation (P = 0.007), oligodendroglioma component (P = 0.010), lower grade (P = 0.005), absence of EGFR amplification (P = 0.021), and longer progression-free survival (HR 0.161, CI 0.037 to 0.704, P = 0.015). Conclusions: In HGGs, uptake of ⁶⁸Ga-DOTA-peptides is associated with disrupted BBB and cannot be predicted by SSTR₂ immunohistochemistry. Thus, PET/CT shows limited value to detect HGGs suitable for PRRT. However, high SSTR₂ expression portends favorable outcome along with established biomarkers such as IDH1 mutation. Trial registration: ClinicalTrials.gov NCT01460706

The aim of this study was to develop a convolutional neural network (CNN) for classifying positron emission tomography (PET) images of patients with and without head and neck squamous cell carcinoma (HNSCC) and other types of head and neck cancer. A PET/magnetic resonance imaging scan with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) was performed for 200 head and neck cancer patients, 182 of which were diagnosed with HNSCC, and the location of cancer tumors was marked to the images with a binary mask by a medical doctor. The models were trained and tested with five-fold cross-validation with the primary data set of 1990 2D images obtained by dividing the original 3D images of 178 HNSCC patients into transaxial slices and with an additional test set with 238 images from the patients with head and neck cancer other than HNSCC. A shallow and a deep CNN were built by using the U-Net architecture for classifying the data into two groups based on whether an image contains cancer or not. The impact of data augmentation on the performance of the two CNNs was also considered. According to our results, the best model for this task in terms of area under receiver operator characteristic curve (AUC) is a deep augmented model with a median AUC of 85.1%. The four models had highest sensitivity for HNSCC tumors on the root of the tongue (median sensitivities of 83.3–97.7%), in fossa piriformis (80.2–93.3%), and in the oral cavity (70.4–81.7%). Despite the fact that the models were trained with only HNSCC data, they had also very good sensitivity for detecting follicular and papillary carcinoma of thyroid gland and mucoepidermoid carcinoma of the parotid gland (91.7–100%).